The goal of the proposed research is to determine the role of a subset of proto-onocogenes in the growth and development of the free-living soil nematode Caenorhabditis elegans. Using viral oncogenes as probes we have isolated and characterized homologs of the vertebrate c-abl, c-src and c-myb genes. We are in the process of characterizing candidates for the c-erbB gene. DNA sequence analysis shows that the amino acid sequence of the C. elegans abl and src proteins is very similar to the homologous vertebrate and Drosophila gene products. We have isolated two C. elegans genes that show protein sequence similarity to the vertebrate c-myb and c-fos gene products. Interestingly, these C. elegans genes, myb-1 and myb-2, have diverged considerably from the corresponding Drosophila and vertebrate genes. A combination of molecular and cytological techniques will be used to pinpoint the time and site of expression of each of these genes during development. Northern analysis has shown that each of these genes is developmentally regulated. A combination of genetic and molecular genetic techniques will be used to identify mutant alleles of these proto-oncogenes. Analysis of the phenotypes associated with these mutants should bring us closer to an understanding of the role of these proto-onco-genes in development of C. elegans. In addition to studying the role of the above proto-oncogenes in C. elegans development, we also propose to continue our analysis of DNA-mediated gene transfer in C. elegans. These studies will be directed towards two goals, to improve current methods for obtaining stable transgenics and to obtain targeted inactivation of specific endogenous genes in C. elegans.